Trifluoroacetic acid → [(1S,5S)-7-Methylene-4-oxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-yl]carboxylic acid

Trifluoroacetic acid (26.0 ml) was added to a solution of [(1S,5S)-7-methylene-4-oxo-3-[(1R)-1-phenylethyl]-3-aza-bicyclo[3.3.0]octan-1-yl]carboxylic acid tert-butyl ester (2.47 g, 8.66 mmol) in dichloromethane (26.0 ml) with stirring under ice-cooling, and the mixture was stirred at room temperature for one hour. The reaction solution was concentrated under reduced pressure, and trifluoroacetic acid was azeotropically distilled with toluene (×3). A 1 mol/l sodium hydroxide solution (15.0 ml) was added to the resulting residue under ice-cooling, and the mixture was washed with diethyl ether (60 ml×2). The aqueous layer was made acidic with 6 mol/l hydrochloric acid (4 ml) under ice-cooling, followed by extraction with ethyl acetate (100 ml×2). The organic layers were combined, washed with water (100 mL) and brine (100 ml), and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure to give 2.15 g of the title compound as white crystals.

1. temperaturecooling
2. stirringthe mixture was stirred at room temperature for one hour
3. concentrationThe reaction solution was concentrated under reduced pressure, and trifluoroacetic acid
4. distillationwas azeotropically distilled with toluene (×3)
5. additionA 1 mol/l sodium hydroxide solution (15.0 ml) was added to the resulting residue under ice-
6. temperaturecooling
7. washthe mixture was washed with diethyl ether (60 ml×2)
8. temperaturecooling
9. extractionfollowed by extraction with ethyl acetate (100 ml×2)
10. washwashed with water (100 mL) and brine (100 ml)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationAfter filtration
13. concentrationthe filtrate was concentrated under reduced pressure

ORD record

ord-8fa5219687fe4b05af0f36ad7b3e023a

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08618094B2